Proc Natl Acad Sci U S A
November 2023
The temporal difference learning (TDL) algorithm has been essential to conceptualizing the role of dopamine in reinforcement learning (RL). Despite its theoretical importance, it remains unknown whether a neuronal implementation of this algorithm exists in the brain. Here, we provide an interpretation of the recently described signaling properties of ventral tegmental area (VTA) GABAergic neurons and show that a circuitry of these neurons implements the TDL algorithm.
View Article and Find Full Text PDFThe striatum and subthalamic nucleus (STN) are considered to be the primary input nuclei of the basal ganglia. Projection neurons of both striatum and STN can extensively interact with other basal ganglia nuclei, and there is growing anatomic evidence of direct axonal connections from the STN to striatum. There remains, however, a pressing need to elucidate the organization and impact of these subthalamostriatal projections in the context of the diverse cell types constituting the striatum.
View Article and Find Full Text PDFNowadays, the use of hybrid structures and multi-component materials is gaining ground in the fields of environmental protection, water treatment and removal of organic pollutants. This study describes promising, cheap and photoactive self-supported hybrid membranes as a possible solution for wastewater treatment applications. In the course of this research work, the photocatalytic performance of titania nanowire (TiO NW)-based hybrid membranes in the adsorption and degradation of methylene blue (MB) under UV irradiation was investigated.
View Article and Find Full Text PDFThe suitability of a new type of polyurethane-based composite carbon foam for several possible usages is evaluated and reported. A comparison of the properties of the as-prepared carbon foams was performed with widely available commercial biomass-derived activated carbon. Carbon foams were synthesized from polyurethane foams with different graphite contents through one-step activation using CO.
View Article and Find Full Text PDFThe striatum mediates a broad range of cognitive and motor functions. Within the striatum, recently discovered tyrosine hydroxylase expressing interneurons (THINs) provide a source of intrastriatal synaptic connectivity that is critical for regulating striatal activity, yet the role of THIN's in behavior remains unknown. Given the important role of the striatum in reward-based behaviors, we investigated whether loss of striatal THINs would impact instrumental behavior in mice.
View Article and Find Full Text PDFOur original review, "Heterogeneity and Diversity of Striatal GABAergic Interneurons," to which this is an invited update, was published in December, 2010 in Frontiers is Neuroanatomy. In that article, we reviewed several decades' worth of anatomical and electrophysiological data on striatal parvalbumin (PV)-, neuropeptide Y (NPY)- and calretinin(CR)-expressing GABAergic interneurons from many laboratories including our own. In addition, we reported on a recently discovered novel tyrosine hydroxylase (TH) expressing GABAergic interneuron class first revealed in transgenic TH EGFP reporter mouse line.
View Article and Find Full Text PDFRecent discoveries of striatal GABAergic interneurons require a new conceptualization of the organization of intrastriatal circuitry and their cortical and thalamic inputs. We investigated thalamic inputs to the two populations of striatal neuropeptide Y (NPY) interneurons, plateau low threshold spike (PLTS) and NPY-neurogliaform (NGF) cells. Optogenetic activation of parafascicular inputs evokes suprathreshold monosynaptic glutamatergic excitation in NGF interneurons and a disynaptic, nicotinic excitation through cholinergic interneurons.
View Article and Find Full Text PDFUnlabelled: Synchronous optogenetic activation of striatal cholinergic interneurons ex vivo produces a disynaptic inhibition of spiny projection neurons composed of biophysically distinct GABAAfast and GABAAslow components. This has been shown to be due, at least in part, to activation of nicotinic receptors on GABAergic NPY-neurogliaform interneurons that monosynaptically inhibit striatal spiny projection neurons. Recently, it has been proposed that a significant proportion of this inhibition is actually mediated by activation of presynaptic nicotinic receptors on nigrostriatal terminals that evoke GABA release from the terminals of the dopaminergic nigrostriatal pathway.
View Article and Find Full Text PDFBackground: Health literacy (HL) is low for 40-50 % of the population in developed nations, and is strongly linked to many undesirable health outcomes. Older adults are particularly at risk. The intervention research on health literacy in ageing populations project systematically created a large inventory of HL interventions targeting adults age 50+ , to support practical production of policy and practice guidelines for promoting health literacy in European populations.
View Article and Find Full Text PDFThe recent electrophysiological characterization of TH-expressing GABAergic interneurons (THINs) in the neostriatum revealed an unexpected degree of diversity of interneurons in this brain area (Ibáñez-Sandoval et al., 2010, Unal et al., 2011, 2015).
View Article and Find Full Text PDFStriatal GABAergic interneurons that express the gene for tyrosine hydroxylase (TH) have been identified previously by several methods. Although generally assumed to be dopaminergic, possibly serving as a compensatory source of dopamine (DA) in Parkinson's disease, this assumption has never been tested directly. In TH-Cre mice whose nigrostriatal pathway had been eliminated unilaterally with 6-hydroxydopamine, we injected a Cre-dependent virus coding for channelrhodopsin-2 and enhanced yellow fluorescent protein unilaterally into the unlesioned midbrain or bilaterally into the striatum.
View Article and Find Full Text PDFPrevious work suggests that neostriatal cholinergic interneurons control the activity of several classes of GABAergic interneurons through fast nicotinic receptor-mediated synaptic inputs. Although indirect evidence has suggested the existence of several classes of interneurons controlled by this mechanism, only one such cell type, the neuropeptide-Y-expressing neurogliaform neuron, has been identified to date. Here we tested the hypothesis that in addition to the neurogliaform neurons that elicit slow GABAergic inhibitory responses, another interneuron type exists in the striatum that receives strong nicotinic cholinergic input and elicits conventional fast GABAergic synaptic responses in projection neurons.
View Article and Find Full Text PDFNeuronal control with high temporal precision is possible with optogenetics, yet currently available methods do not enable to control independently multiple locations in the brains of freely moving animals. Here, we describe a diode-probe system that allows real-time and location-specific control of neuronal activity at multiple sites. Manipulation of neuronal activity in arbitrary spatiotemporal patterns is achieved by means of an optoelectronic array, manufactured by attaching multiple diode-fiber assemblies to high-density silicon probes or wire tetrodes and implanted into the brains of animals that are expressing light-responsive opsins.
View Article and Find Full Text PDFNeostriatal cholinergic interneurons are believed to be important for reinforcement-mediated learning and response selection by signaling the occurrence and motivational value of behaviorally relevant stimuli through precisely timed multiphasic population responses. An important problem is to understand how these signals regulate the functioning of the neostriatum. Here we describe the synaptic organization of a previously unknown circuit that involves direct nicotinic excitation of several classes of GABAergic interneurons, including neuroptide Y-expressing neurogilaform neurons, and enables cholinergic interneurons to exert rapid inhibitory control of the activity of projection neurons.
View Article and Find Full Text PDFWe investigated the properties of neostriatal neuropeptide Y (NPY)-expressing interneurons in transgenic GFP (green fluorescent protein)-NPY reporter mice. In vitro whole-cell recordings and biocytin staining demonstrated the existence of a novel class of neostriatal NPY-expressing GABAergic interneurons that exhibit electrophysiological, neurochemical, and morphological properties strikingly different from those of previously described NPY-containing, plateau-depolarization low-threshold spike (NPY-PLTS) interneurons. The novel NPY interneuron type (NPY-neurogliaform) differed from previously described NPY-PLTS interneurons by exhibiting a significantly lower input resistance and hyperpolarized membrane potential, regular, nonaccommodating spiking in response to depolarizing current injections, and an absence of plateau depolarizations or low-threshold spikes.
View Article and Find Full Text PDFAlthough the notion that dopaminergic neurons utilize glutamate as a co-transmitter has long been supported by tantalizing molecular, immunocytochemical and electrophysiological evidence it has only been with the recent addition of optogenetic and other approaches that the existence and functional relevance of this mechanism could be unambiguously demonstrated. Here we discuss the possible mechanisms of action of glutamate released from mesoaccumbens dopaminergic neurons based on recently accumulated evidence. Surprisingly, rather then to confirm a role in conventional fast excitatory transmission, the latest evidence suggests that glutamate released from dopaminergic neurons may primarily act through different unconventional presynaptic and postsynaptic mechanisms.
View Article and Find Full Text PDFThe canonical view of striatal GABAergic interneurons has evolved over several decades of neuroanatomical/neurochemical and electrophysiological studies. From the anatomical studies, three distinct GABAergic interneuronal subtypes are generally recognized. The best-studied subtype expresses the calcium-binding protein, parvalbumin.
View Article and Find Full Text PDFRecent evidence suggests the intriguing possibility that midbrain dopaminergic (DAergic) neurons may use fast glutamatergic transmission to communicate with their postsynaptic targets. Because of technical limitations, direct demonstration of the existence of this signaling mechanism has been limited to experiments using cell culture preparations that often alter neuronal function including neurotransmitter phenotype. Consequently, it remains uncertain whether glutamatergic signaling between DAergic neurons and their postsynaptic targets exists under physiological conditions.
View Article and Find Full Text PDFWhole-cell recordings were obtained from tyrosine hydroxylase-expressing (TH(+)) neurons in striatal slices from bacterial artificial chromosome transgenic mice that synthesize enhanced green fluorescent protein (EGFP) selectively in neurons expressing TH transcriptional regulatory sequences. Stereological cell counting indicated that there were approximately 2700 EGFP-TH(+) neurons/striatum. Whole-cell recordings in striatal slices demonstrated that EGFP-TH(+) neurons comprise four electrophysiologically distinct neuron types whose electrophysiological properties have not been reported previously in striatum.
View Article and Find Full Text PDFRecent studies have demonstrated that GABAergic synaptic transmission among neostriatal spiny projection neurons (SPNs) is strongly modulated by dopamine with individual connections exhibiting either D(1) receptor (D(1)R)-mediated facilitation or D(2) receptor (D(2)R)-mediated inhibition and, at least in some preparations, a subset of connections exhibiting both of these effects. In light of the cell type-specific expression of D(1a)R in striatonigral and D(2)R in striatopallidal neurons and the differential expression of the other D(1) and D(2) family dopamine receptors, we hypothesize that the nature of the dopaminergic modulation is specific to the types of SPNs that participate in the connection. Here the biophysical properties and dopaminergic modulation of intrastriatal connections formed by striatopallidal neurons were examined.
View Article and Find Full Text PDFThere are two distinct inhibitory GABAergic circuits in the neostriatum. The feedforward circuit consists of a relatively small population of GABAergic interneurons that receives excitatory input from the neocortex and exerts monosynaptic inhibition onto striatal spiny projection neurons. The feedback circuit comprises the numerous spiny projection neurons and their interconnections via local axon collaterals.
View Article and Find Full Text PDFIntroduction: Authors made 162 knee arthroscopic operations due to hemarthrosis of the knee, acute knee blocking or acute developed instability on patients under 18 years after knee injury during a 12 years period. The retrospective analysis of patient reports shows, that in 61.7% of the cases they found chondral- or osteochondral fracture in the knee.
View Article and Find Full Text PDFATP-sensitive K+ (K(ATP)) channels link metabolic state to cell excitability. Here, we examined regulation of K(ATP) channels in substantia nigra dopamine neurons by hydrogen peroxide (H2O2), which is produced in all cells during aerobic metabolism. Blockade of K(ATP) channels by glibenclamide (100 nM) or depletion of intracellular H2O2 by including catalase, a peroxidase enzyme, in the patch pipette increased the spontaneous firing rate of all dopamine neurons tested in guinea pig midbrain slices.
View Article and Find Full Text PDFThe vast majority of neostriatal neurons and intrinsic intrastriatal synapses are GABAergic, the latter arising from axon collaterals of spiny projection neurons and from GABAergic interneurons. An important feature of the functional organization of the neostriatum has long been assumed to be the existence of a widespread lateral inhibitory network mediated by the axon collaterals of spiny projection neurons. However, these collateral connections have recently been demonstrated electrophysiologically to be relatively weak--in contrast to feedforward interneuronal inhibition, which exerts strong effects on spike timing in spiny neurons.
View Article and Find Full Text PDFMost neurons in the neostriatum are GABAergic spiny projection neurons with extensive local axon collaterals innervating principally other spiny projection neurons. The other source of GABAergic inputs to spiny neurons derives from a small number of interneurons, of which the best characterized are the parvalbumin-containing, fast-spiking interneurons. Spiny neuron collateral inhibition was not demonstrated until recently, because the IPSPs recorded at the soma are surprisingly small.
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